TY - JOUR
T1 - Neural crest cell origin and signals for intrinsic neurogenesis in the mammalian respiratory tract
AU - Langsdorf, Aliete
AU - Radzikinas, Kelsi
AU - Kroten, Amanda
AU - Jain, Sanjay
AU - Ai, Xingbin
PY - 2011/3/1
Y1 - 2011/3/1
N2 - Our study investigates the innervation of the respiratory tract during mouse embryonic development, with a focus on the identification of cell origin and essential developmental signals for the resident, or intrinsic, neurons. Using lineage tracing, we show that these intrinsic neurons are exclusively derived from neural crest cells, and cluster to formganglia that reside in the dorsal trachea andmedial bronchiwith diminishing frequency. Comparisons of intrinsic neurogenesis between wild-type, glial cell-derived neurotrophic factor (GDNF)-/-, neurturin-/-, and tyrosine kinase receptor Ret-/- embryos, in combination with lung organ cultures, identified that Ret signaling, redundantly activated by GDNF family members, is required for intrinsic neurogenesis in the trachea and primary bronchi. In contrast, Ret deficiency exerts no effect on the innervation of the rest of the respiratory tract, suggesting that innervation by neurons whose cell bodies are located outside of the lung (so-called extrinsic neurons) is independent of Ret signaling. Furthermore, although the trachea, the esophagus, and their intrinsic neurons share foregut endoderm and a neural crest cell origin, respectively, the signals required for their intrinsic neurogenesis are divergent. Together, our results not only establish the neural crest lineageof intrinsicneurons in the respiratory tract, but also identify regional differences in the abundance and developmental signals of intrinsic neurons along the respiratory tract and in the esophagus.
AB - Our study investigates the innervation of the respiratory tract during mouse embryonic development, with a focus on the identification of cell origin and essential developmental signals for the resident, or intrinsic, neurons. Using lineage tracing, we show that these intrinsic neurons are exclusively derived from neural crest cells, and cluster to formganglia that reside in the dorsal trachea andmedial bronchiwith diminishing frequency. Comparisons of intrinsic neurogenesis between wild-type, glial cell-derived neurotrophic factor (GDNF)-/-, neurturin-/-, and tyrosine kinase receptor Ret-/- embryos, in combination with lung organ cultures, identified that Ret signaling, redundantly activated by GDNF family members, is required for intrinsic neurogenesis in the trachea and primary bronchi. In contrast, Ret deficiency exerts no effect on the innervation of the rest of the respiratory tract, suggesting that innervation by neurons whose cell bodies are located outside of the lung (so-called extrinsic neurons) is independent of Ret signaling. Furthermore, although the trachea, the esophagus, and their intrinsic neurons share foregut endoderm and a neural crest cell origin, respectively, the signals required for their intrinsic neurogenesis are divergent. Together, our results not only establish the neural crest lineageof intrinsicneurons in the respiratory tract, but also identify regional differences in the abundance and developmental signals of intrinsic neurons along the respiratory tract and in the esophagus.
KW - Extrinsic innervation
KW - GDNF
KW - Intrinsic neuron
KW - Neural crest cell
KW - Respiratory tract
UR - http://www.scopus.com/inward/record.url?scp=79952210266&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2009-0462OC
DO - 10.1165/rcmb.2009-0462OC
M3 - Article
C2 - 20139349
AN - SCOPUS:79952210266
SN - 1044-1549
VL - 44
SP - 293
EP - 301
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
IS - 3
ER -